POS0777 STUDY OF PERIPHERAL BLOOD B CELL IMMUNO-PHENOTYPING IN PATIENTS WITH LUPUS NEPHRITIS: PARAMETERS OF DISEASE ACTIVITY, REMISSION AND FLARE
Authors: C. Di Mario, V. Varriano, L. Petricca, A. Paglionico, M. R. Gigante, S. Costanzi, L. Bui, F. Federico, M. A. D’agostino, S. Alivernini, B. Tolusso, E. Gremese
Journal: Annals of the Rheumatic Diseases (2022)

Background B cells play a central role in systemic lupus erythematosus (SLE) pathogenesis connecting innate with adaptative immunity. Objectives To investigate the peripheral blood B cell phenotype in a cohort of SLE patients with renal involvement (LN-SLE) in relation to disease activity and renal histological lesions compared to healthy controls. Methods One hundred LN-SLE patients with active renal involvement, 40 at disease onset (Early) and 60 in whom LN occurred after the disease onset (Long) were enrolled. Thirty-seven healthy controls were included. Clinical, laboratory and demographic data were collected at baseline and at 6 and 12 month of follow-up. Disease activity was recorded using SLEDAI-2K. Ultrasound-guided renal biopsy has been performed for the definition of the nephritic class according to the ISN/RPS classification. The memory B cells immunophenotyping (IgD/CD27 classification) was analyzed in peripheral blood through flow cytometry. To clarify the role of key molecules in the B cells activation, IL-6 and BAFF serum levels were assayed by Enzyme-linked immunosorbent assay (ELISA). Results According to the onset of renal symptoms, there were no differences in the distribution of the renal classes and in activity and chronicity indices in the two groups. A direct correlation was observed between chronicity index score and creatinine in the whole cohort (R=0.342; p &lt; 0.01 ) and in LN-SLE Early (R=0.528; p = 0.01 ) and Long (R=0.337; p=0.02 ). The disease activity index was found to be significantly higher in anti-dsDNA positive than in negative ones (6.6±4.8 vs 2.8±3.5; p=0.01 ), and in patients with at least one antiphospholipid antibody-APL positivity (6.8±4.8 vs 5.1±4.8; p=0.05 ). Considering predictive biomarkers of the remission within 12 months, the presence of histological lesions (glomerulosclerosis and fibrocellular crescents) and the positivity for at least one of the APL antibodies were associated to the failure in achieving clinical remission, while baseline 24h-UP levels ≤2750mg were associated to remission achievement [OR:2.6(95%CIs:1.1-5.8)]. Studying the B cells subset, a lower percentage of CD19 pos and unswitched memory (IgD pos CD27 pos ) in LN-SLE compared to controls (6.8±5.5% vs 10.5±3.5%; p&lt;0.01 and 11.1±12.0% vs 15.3±8.0%; p &lt; 0.01, respectively) was observed. In addition, we found higher levels of double-negative memory B cells (IgD neg CD27 neg ) and plasmablasts (CD27 pos CD38 pos ) in LN-SLE than in controls [(CD27 neg IgD neg 10.0±8.7% vs 4.1±1.9%; p&lt;0.01 )(CD27 pos CD38 pos 4.4±5.3% vs 1.0±0.5%; p &lt; 0.01 )]. Furthermore, CD19 pos and IgD pos CD27 pos negatively correlated with BAFF [(R=-0.327; p=0.03 and R=-0.305; p=0.04 ) respectively] while a direct correlation was observed between IgD neg CD27 neg B cells and IL-6 serum levels (R=0.302; p &lt;0.01). No correlation was found between B cells subsets and the disease activity parameters. Considering the remission status achievement within 12 months both LN-SLE groups had significantly lower frequencies of IgD pos CD27 pos than controls [(Remission:10.7±12.4% vs 15.3±8.0%; p &lt; 0.01 )(No-Remission:9.8±9.5% vs 15.3±8.0%; p &lt; 0.01 )] conversely had a significantly higher rate of IgD neg CD27 neg than controls [(Remission:11.5±10.0% vs 4.1±1.9%; p &lt; 0.01 ;NoRemission:9.6±6.7% vs 4.1±1.9%; p &lt; 0.01 ] and plasmablasts [(Remission 5.2±6.7% vs 1.0±0.5; p=0.05; NoRemission:4.1±3.4 vs 1.0±0.5; p&lt;0.01 )] Conclusion This study suggests that the active injury and chronic damage histological features of LN do not depend on the SLE duration per se , but could be associated to the failure in achieving clinical remission within 12 months. Furthermore, data on memory B cells immunophenotyping reveals a distinct B cells subset of SLE patients when compared to healthy controls, confirming an alteration of B cells subsets in SLE patients and strengthening the hypothesis of the pathogenetic role played by B lymphocytes in the course of LN. References [1]Obris că et al . Int J Mol Sci 2021;22(7):3766. [2]Zhu L et al. Clin Rheumatol 2018;37(1):205-212. Disclosure of Interests None declared